Sensitivity analysis of signaling pathways based on frequency distribution of the model step response

The paper deals with sensitivity analysis of signaling pathway models. Though the sensitivity methods are well known, their application to various models is always based on the assumption that the output of the system whose sensitivity is analyzed is given by absolute quantitative data. In signaling pathways models, however, direct measurement of concentrations is not feasible and such data is always normalized. This may skew conclusions stemming from standard sensitivity analysis. Here we propose a method based on frequency distribution of a system time response that overcomes constraints imposed by experimental methods. We illustrate its applicability with a novel model of interactions between two stress induced signalling pathways, activated by TNF and heat shock.